tbuckley/cabot-search huggingface dataset:
BAYONET trial: A multicenter phase II trial of staged combination with encorafenib + binimetinib + cetuximab following encorafenib + cetuximab in patients with<i> BRAF</i> V600E-mutant metastatic colorectal cancer.
Authors: Yuki Matsubara, Hideaki Bando, Daisuke Kotani, Yoshinori Kagawa, Kazuaki Harada, Hiroki Osumi, Naoki Izawa, Takeshi Kawakami, Shogen Boku, Toshihiko Matsumoto, Masashi Wakabayashi, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2023)

TPS271 Background: While the triplet combination of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CET) indicated higher response rate compared to the doublet combination of ENCO + CET, no significant survival benefits of the triplet combination were observed in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC) according to BEACON CRC study. Although ENCO + CET is the standard 2 nd -line therapy in the United States and European Union, poor prognoses are expected after disease progression. As resistant mechanisms of BRAF + EGFR blockage, several MAPK pathway alternations, including RAS and RAF mutations were reported, which suggests the additional blockade of MAPK signaling may be an effective strategy for ENCO + CET refractory mCRC. In addition, the preclinical study suggested BRAF inhibitor + anti-EGFR antibody resistant BRAF V600E-mutant colorectal cancer cell-lines were sensitive to the combination of BRAF inhibitor + MEK inhibitor + anti-EGFR antibody (Oddo D, et al. Cancer Res. 2016). Methods: BAYONET is a single-arm multicenter phase II trial to evaluate the efficacy and safety of the staged combination with ENCO + BINI + CET for patients with BRAF V600E-mutant mCRC who were refractory to ENCO + CET. The main eligibility criteria are as follows; RAS wild-type/ BRAF V600E-mutant mCRC; age ≥ 20; ECOG PS 0 or 1; within 4 weeks from the last administration of previous ENCO or CET; no administration of other systemic therapy after refractoriness to ENCO + CET; complete response, partial response, or ≥4 months of stable disease were observed in the previous ENCO + CET. Included patients receive the combination treatment of ENCO (300mg once a day) + BINI (45mg twice a day) + CET (400mg/m 2 initial dose and then 250mg/m 2 once a week) in a 28 day-cycle as a study treatment. The primary endpoint of this trial is 12-week progression-free survival (PFS) rate. The secondary endpoints include PFS, overall survival, objective response rate, disease control rate, time to treatment failure, and the incidence of adverse events. The targeted sample size was calculated to be 30 on the basis of a power of 80%, a significant level of 10% (one-sided), the threshold 12-week PFS rate of 20%, and the expected 12-week PFS rate of 40%. As a translational analysis, circulating tumor DNA for next-generation sequencing using Guardant360 is collected at twice time points (before and after study treatment) to investigate the resistance mechanisms. Enrollment started from Jan 2022 and is ongoing at 25 facilities in Japan. As of Sep 20, 2022, 9 patients were enrolled. Clinical trial information: jRCTs031210510 .
A phase II study to evaluate anlotinib plus TQB2450 as adjuvant therapy in patients with esophageal squamous cell carcinoma (ALTER-E005).
Authors: Changying Guo, Shengjia Chen, Yongqiang Ye, Wei-Min Mao
Journal: Journal of Clinical Oncology (2023)

TPS488 Background: About 30.3-58.0% of patients who undergo esophagectomy may experience recurrence. The efficacy of postoperative chemoradiation has not been demonstrated in a randomized trial in patients with esophageal squamous cell carcinoma (ESCC) compared to surgery along. Therefore, it is urgent to explore more effective and safer postoperative regimen for resectable ESCC. Checkmate 577 has demonstrated immunotherapy can prolong disease free survival (DFS) for patients who have residual disease following preoperative chemoradiation and R0 resection. Anlotinib is an orally administered tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4 and PDGFRα/β. In a randomized, double-blind phase 2 trial, the use of anlotinib in previously treated metastatic ESCC patients significantly improved progression-free survival (PFS) compared with placebo ( NCT02649361 ). TQB2450 is a novel humanized monoclonal antibody against PD-L1, which has shown encouraging activity in combination with anlotinib in the treatment of multiple tumors, such as biliary tract cancer (NCT03996408) and ovarian cancer (NCT04236362). The ALTER-E005 study is designed to evaluate the efficacy and safety of anlotinib combined with TQB2450as adjuvant therapy in ESCC patients. Methods: ALTER-E005 is a multi-center, single-arm, phase II study. A total of 30 patients will be enrolled. Eligible pts (≥18 years) must be histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC; received radical (R0) resection of ESCC with no recurrence in imaging examination within 6-12 weeks after surgery; ECOG PS 0–1. Patients enrolled will receive oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1,200 mg on day 1 every 3 weeks until disease recurrence. The primary endpoint is DFS. The secondary endpoints include safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Enrollment to the ALTER-E005 trial is currently ongoing in China. Clinical trial information: NCT05252078 .
Liver-directed combined radiotherapy for downstaging of over the Milan advanced hepatocellular carcinoma converting to liver transplantation.
Authors: Yong Tae Kim, Jae Geun Lee, Jinsil Seong
Journal: Journal of Clinical Oncology (2023)

561 Background: Recent success of combined immunotherapy sheds a light to the future of advanced hepatocellular carcinoma patients but still remains as a palliative setting. The best oncologic outcome for HCC can be obtained by curative surgery either by resection or liver transplantation (LT). Efficacy of liver-directed combined radiotherapy (LD-CRT) for downstaging and subsequent surgical resection in locally advanced HCC had been reported earlier by our team. In this study, we investigated the role of LD-CRT as a downstaging strategy for converting advanced hepatocellular carcinoma to LT. Methods: We reviewed 55 hepatocellular carcinoma patients who had undergone downstaging LD-CRT and subsequent liver transplantation from January 2009 to February 2022. Patients within Milan criteria at the time of receiving radiotherapy were excluded and clinical characteristics and histopathology of explant liver were evaluated. The overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: The median follow-up period was 48.6 months (range 6.9 – 151.7 months). Of 55 patients, 24 (43.6%) were treatment naïve. At the time of RT, 36 patients presented large tumor (tumor diameter &gt;5 cm) or multiple lesions (&gt;3 lesions), 37 with major vessel involvement or portal vein tumor thrombosis, and 7 with extrahepatic lesion. LD-CRT was given as localized concurrent chemoradiation (CCRT) for 41 patients (74.5%) and transarterial chemoembolization (TACE) plus RT for 10 patents (18.2%). Substantial downstaging has been achieved in 38 (69%) patients with initially over the Milan to within Milan. Specifically, 29 of 37 patients initially with major vessel invasion or with tumor thrombosis were successfully converted to microscopic vessel invasion or tumor thrombus-free status in explant liver. 5-year overall survival was 68.1% and 2-year disease-free survival was 51%, respectively. Recurrence after transplantation was observed in 18 patients(4 intrahepatic recurrence and 14 extrahepatic metastasis) and the majority (14/18) occurred within 2 years. Conclusions: Liver-directed combined radiotherapy as a downstaging strategy for liver transplantation achieved favorable oncologic outcomes in advanced hepatocellular carcinoma patients. This study suggests that active adoption of radiotherapy needs full consideration for locally advanced HCC patients, opening a chance for curative LT.
Impact of high-dose dexamethasone and prolonged infusion time to prevent hypersensitivity reaction related to oxaliplatin in patients with colorectal cancer.
Authors: Koichiro Yoshino, Hiroki Osumi, Akira Ooki, Koshiro Fukuda, Shota Fukuoka, Izuma Nakayama, Takeru Wakatsuki, Mariko Ogura, Daisuke Takahari, Keisho Chin, Kensei Yamaguchi, Eiji Shinozaki
Journal: Journal of Clinical Oncology (2023)

49 Background: Oxaliplatin (OXA) is one of the major cytotoxic agents for the treatment of gastrointestinal tumors. Hypersensitivity reaction (HSR) is one of major reasons of not continuing OXA-based chemotherapy, similar to chemotherapy-induced peripheral neuropathy (CIPN). We developed prevention of the HSR protocol and evaluated its clinical application. Methods: We have retrospectively evaluated and characterized HSR reaction in metastatic colorectal cancer patients exposed to an OXA-containing regimen between 2005 and 2019. We also evaluated the clinical utility of a prevention of the HSR protocol for mCRC patients occurred in grade 1, grade 2 or grade 3 HSR after administration of OXA-based chemotherapy. The prevention of HSR protocol is based on increasing the dose of dexamethasone to 16.5 mg/body, chlorpheniramine to 5 mg, famotidine to 20mg, and the administration time of OXA is extended to 4 hours. Results: A total of 209 patients (median age 61 years, range: 27 to 80) were experienced grade 1 (106 patients, 50.7%), grade 2 (98 patients, 46.0%), or grade 3 HSR (5 patients, 3.3%). Most of the patients had been treated with the FOLFOX4 or modified FOLFOX6 regimen (86.6%). The median number of cycles of OXA administration until the initial onset of HSR was 11 (range: 2 to 48). 111 patients (53.1%) succeeded in OXA re-administration under the prevention of HSR protocol. The median OXA free interval was 23 days (range: 13 to 890). The median progression-free survival after OXA re-administration was 7.0 months (95%CI: 5.3 to 10.4). The reason for the prevention of HSR protocoldiscontinuation was HSR in 98 patients (46.9%), disease progression in 77 patients (36.9%) and CIPN in 17 patients (8.1%), respectively. Forty-eight patients (49.0%) had HSR during the first cycle of OXA re-administration and the median time to HSR after OXA re-administration was 14 days (95%CI 0-19). Grade 3 HSR after OXA re-administrationwere observed in only 6 patients (6.1%) and no one experienced Grade 4 or 5 HSR. Conclusions: Hi-dose dexamethasone and an increased infusion time may allow for OXA re-administration. The prevention of the HSR protocol may provide an alternative to permanent discontinuation of OXA.
Comparison of treatment utilization and clinical outcomes among elderly patients with colon cancer from a limited-resource and high-resource setting.
Authors: Joanna El Hajj, Aravind Sanjeevaiah, Radhika Kainthla, Salwan Al Mutar, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2023)

20 Background: Elderly colon cancer patients face unique age-specific challenges during their treatments. The resource availability at the healthcare facility can affect their cancer-related outcomes. We evaluated the utilization of therapies and compared outcomes among elderly colon cancer patients treated in a limited-resource versus a high-resource healthcare setting. Methods: Patients &gt;70 years of age with stage II-IV colon adenocarcinoma diagnosed between 2011 and 2017 were identified from the tumor registry of a large safety-net hospital (limited-resource setting), and an NCI-designated Comprehensive Cancer Center (high-resource setting). We compared the frequencies of categorical variables using Chi-square and Fisher’s exact tests and used a t-test to compare continuous variables between the limited-resource and high-resource setting patients. A multivariate survival analysis was performed using the Cox proportional hazard models adjusting for age, race/ethnicity [Hispanic, non-Hispanic White (NHW), and non-Hispanic Black (NHB)], BMI (&lt;18.5 and &gt; 18.5), gender, hospital setting (limited-resource vs. high-resource setting), staging (II, III, and IV), laterality of the tumor (right or left) and performance of surgery. Results: One-hundred-twenty-one elderly colon cancer patients were identified; the median age at diagnosis was 75 years (IQR 72-80.5), predominantly females (53%). Fifty-four patients (44.6%) received treatment in the limited-resource setting while sixty-seven (55.4%) were treated in the high-resource setting. Most patients were NHW (46%), followed by NHB (25%) and Hispanics (23%). Hispanic patients were more frequent in the limited-resource setting (44% vs 6%) while NHW were more frequent in the high-resource setting (73.8% vs. 14.8%). Utilization of surgery (83% vs. 85%, p-value = 0.8), the use of adjuvant chemotherapy for stage III colon cancer (34.8% vs. 65.2%; p-value = 0.295) and palliative chemotherapy among stage IV (39% vs. 61%; p-value = 0.5) was not significantly different among the elderly patients treated in the limited-resource setting as compared to high-resource setting. On the multivariate survival analysis, stage IV disease (p-value = 0.002) and limited-resource setting (HR = 0.37, 95% CI = 0.19-0.71, p-value = 0.003) were independently associated with survival in this cohort. Conclusions: Elderly patients treated in the limited-resource setting had lower survival as compared to those treated in the high-resource setting. There was a trend toward lower utilization of chemotherapy for stage III and IV elderly colon cancer patients in the limited-resource setting compared to the high-resource setting. The patient or system-related factors that may contribute to this disparity should be further explored.
The impact of relative dose intensity on overall and progression-free survival during cabozantinib therapy for unresectable hepatocellular carcinoma.
Authors: Tsubasa Nobusawa, Kaoru Tsuchiya, Yutaka Yasui, Naoki Uchihara, Keito Suzuki, Yuki Tanaka, Haruka Miyamoto, Shun Ishido, Michiko Yamada, Taisei Keitoku, Hiroaki Matsumoto, Mayu Higuchi, Kenta Takaura, Shohei Tanaka, Chiaki Maeyashiki, Nobuharu Tamaki, Hiroyuki Nakanishi, Masayuki Kurosaki, Namiki Izumi
Journal: Journal of Clinical Oncology (2023)

569 Background: Cabozantinib (CAB) has been approved as 2 nd or later-line worldwide in patients with unresectable hepatocellular carcinoma (u-HCC). There is no data about the relationship between the relative dose intensity (RDI) of CAB and clinical outcome. We investigated the impact of RDI on overall survival (OS) and progression-free survival (PFS) during CAB in real-world practice. Methods: A total of 38 u-HCC patients who received CAB between Jan 2021 and Sep 2022 at our institution were enrolled. Tumor assessments in accordance with RECIST ver1.1 were done using dynamic CT or MRI within 4-8 weeks and every 8-10 weeks thereafter. The RDI of CAB for the first month (1M-RDI) was calculated. Results: The median age was 74 years, and 30 patients were Child-Pugh A. BCLC stage A/B/C were 0/ 11/ 27 patients, and 34 patients were previously received atezolizumab plus bevacizumab. As 2 nd or 3 rd -line, 20 patients received CAB. The median follow-up duration was 7.2 months, and the median PFS was 4.4 months in all patients. The median overall survival (OS) was 16.2 months from the administration of CAB. The objective response rate (ORR) and disease control rate (DCR) was 13.8% and 89.7%. Adverse events (AEs) were observed in all patients, requiring dose reduction in 26 patients (68%) and interruption of CAB in 21 patients (55%). The median 1M-RDI was 35%, and there was no significant difference in PFS between 1M-RDI ≧40% (high 1M-RDI, n=13) and &lt;40% (n=16) (4.1 months vs. 4.7 months, p=0.89). There were no significant differences in age, pretreatment ALBI score, AFP, and major vascular invasion (MVI) between the patients with and without a high RDI. The induction rate of molecular targeted therapies after CAB was 60%. The only significant factor associated with PFS was MVI (HR 0.10, 95%CI 0.02-0.65, p=0.02). In a multivariate analysis, pretreatment ALBI score (HR 5.8, 95% CI 1.2-27.8, P=0.03) and hypertension as AE during CAB (HR 0.29, 95% CI 0.09-0.87, P=0.03) were the significant factors associated with OS. Conclusions: Maintaining a high 1M-RDI of CAB was not associated with OS and PFS in real-world practice. Dose modification is essential for CAB therapy in u-HCC patients.
Association of patient and disease characteristics with outcomes of regorafenib in patients with metastatic colorectal cancer.
Authors: Ronan Wenhan Hsieh, Matthew Lee, Devin Johnson, Chenxin Zhang, Jee-Young Moon, Dennis Hsu, Ana Acuna-Villaorduna, Chaoyuan Kuang
Journal: Journal of Clinical Oncology (2023)

135 Background: Regorafenib (rego) is a multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC). No predictive biomarkers have been identified for rego. We conducted a real-world multi-institutional retrospective study to identify the patient and tumor characteristics associated with outcomes of rego in mCRC patients. Methods: Patients from University of Pittsburgh Medical Center and Montefiore Medical Center who received rego for mCRC were included. Patient characteristics, tumor pathology and molecular profiles, treatment history, and response to rego were collected. Primary and secondary outcomes were best objective response and progression free survival (PFS) on rego, respectively. Univariate and multivariate analyses were conducted using Fisher’s exact test, Mann-Whitney U test, Firth logistic regression and Cox proportional-hazards model. Results: 76 patients were included (median age 64, 42% females, 84% whites). Rego yielded a disease control rate of 32% (including 2 complete responses) and a median PFS of 3.6 months. Tumors with high microsatellite instability (MSI-H) had a significantly lower odds of progression of disease (POD) as best objective response (p = 0.01) and a significantly longer median PFS (p = 0.022) compared with tumors with microsatellite stability (MSS) in multivariable models (Table). 75% of MSI-H mCRC patients had not received immunotherapy (IO) prior to rego. Presence of peritoneal carcinomatosis and older age were associated with higher odds of POD (p = 0.093) and a significantly shorter PFS (p = 0.029), respectively. Compared to Whites, Black patients had a numerically higher odds of POD and shorter PFS. Sex, smoking, alcohol, sidedness of CRC, previous treatments, organs involved, and KRAS mutation were not associated with treatment response or PFS. Conclusions: Our study showed that MSI-H mCRC was associated with significantly better response to rego and PFS, even in the absence of prior IO. Other predicting factors for worse outcomes of rego included older age, and potentially peritoneal carcinomatosis and Black race. None of the mutations was found associated with treatment outcomes, with the limitation of lack of comprehensive molecular testing in many patients. Studies to further examine potential biomarkers such as MCL-1 and FBW7 mutations and correlation to clinical outcomes are ongoing. [Table: see text]
Survival and clinical characteristics of patients with colorectal cancer and brain metastases.
Authors: Caroline Gordon, Michael Cecchini, Jill Lacy
Journal: Journal of Clinical Oncology (2023)

29 Background: Brain metastases (BM) are rare in colorectal cancer (CRC) with 1-3% of patients developing BM over their lifetime. There are no screening recommendations for BM in patients with CRC and most are diagnosed after a patient develops symptoms. Identifying the clinical characteristics for patients with CRC and BM may aid clinicians to consider BM early in symptom onset and potentially screen appropriate patients. Methods: We performed a retrospective chart review of patients &gt;18 years diagnosed with CRC and BM at Yale New Haven Hospital from 1/2012-9/2021. Clinical characteristics were analyzed by descriptive statistics, time intervals were compared using the Mann-Whitney test, and survival analysis was done using the Kaplan-Meier method. Results: We identified 93 patients with CRC and BM. Median age at diagnosis was 56 years, 55% were male, 75% of patients had a left sided primary tumor and 47% were rectal primary. At initial diagnosis, 38% and 39% were stage III and IV respectively. RAS/RAF mutations were present in 45% of patients and all were mismatch repair proficient. The median time from CRC diagnosis to BM was 3.81 years (95% CI 3.09, 4.41) and median time from metastatic CRC to BM was 2.21 years (95% CI 1.48, 2.75). Median overall survival after developing BM was 0.49 years (95% CI 0.24, 0.70). Patients with RAS/RAF mutations had a decreased median time from CRC diagnosis to BM of 3.33 years (95% CI 2.69, 4.37) compared to RAS/RAF wildtype at 5.09 years (95% CI 4.44, 7.97) (p 0.0028). Median time to BM from CRC diagnosis was also decreased in females (p 0.01). The location of primary tumor did not significantly decrease time to BM. Prior to BM diagnosis, 76% of patients had lung metastasis. 84% of patients received treatment for BM while 14% had no BM treatment and 2% were unknown. For treatment 50% had Gamma Knife Radiosurgery, 22% underwent surgical excision +/- adjuvant radiation, and 12% underwent whole brain radiotherapy. After BM treatment, 43% of patients received additional chemotherapy. Conclusions: Although BM in CRC is uncommon, early diagnosis in those at risk is critical given the urgent nature of BM. Patients with CRC that develop BM frequently have tumors that originate in the left side of the colon and preexisting lung metastasis. In patients with CRC and BM, the majority develop BM &gt; 3 years after initial CRC diagnosis, and BM onset is significantly shorter in females and patients with tumors harboring a RAS/RAF mutation. After BM diagnosis and treatment, less than half of patients are able to receive subsequent therapy, and median survival is &lt; 6 months. [Table: see text]